This invention concerns optically active (resolved) tert-alkyl pyrrolidinyl heptanoate intermediates which are useful for making biologically active 8-azaprostanoids.
There is relatively little art concerned with optically active 8-azaprostanoids. U.S. Pat. No. 4,113,873 (Himizu) discloses the laevo 15.alpha.-isomer of ##STR1## where R' is ethyl or n-propyl, or a pharmaceutically acceptable salt thereof. Also described is a process for preparing said isomer starting with the aldehyde: ##STR2## where R.sup.4 is lower alkyl. The optically-active (d and l) isomers of this aldehyde are prepared by several reactions starting from d- or l-5-hydroxymethyl-2-pyrrolidone.
U.S. Pat. No. 4,177,346 (Nelson) discloses ##STR3## where A is a single or cis double bond. W is a tetrazol, R.sub.3 is H, or alkyl of 1 to 5 carbons, and R.sub.2 is phenyl. This patent discloses optically active 8-azaprostanoids: ##STR4## and their preparation from d or l-pyroglutamic acid. The synthetic sequence is similar to that used in the Himizu patent in that it also goes through the optically-active 5-hydroxymethyl-2-pyrrolidone.
U.S. Pat. No. 3,975,399 (De Franco and Scribner) describes various 8-azaprostanoids but does not discuss either stereoisomers or optical activity of any of the prostanoids or their intermediates. The racemic 8-azaprostanoids of the patent do not have the optical activity of the 8-azaprostanoids described herein, nor do they possess the biological properties which are a concomitant of said optical activity.
General methods for resolving racemates are discussed in the literature, for example, in "Advanced Organic Chemistry", Fieser and Fieser, Reinhold Publishing Company, 1961, pages 85 to 89; and "Organic Chemistry", Cram and Hammond, 2nd edition, 1964, McGraw-Hill, pages 174 to 176.